tbuckley/cabot-search huggingface dataset:
POS1490-HPR INVESTIGATION OF THE RELATIONSHIP BETWEEN EXERCISE CAPACITY AND PSYCHOSOCIAL VARIABLES IN WOMEN WITH FIBROMYALGIA: A PRELIMINARY STUDY
Authors: B. Beyrek, M. Köprülüoğlu, K. Nas, İ. Naz
Journal: Annals of the Rheumatic Diseases (2022)

Background Various studies have showed that patients with fibromyalgia have lower exercise capacity than healthy individuals (1, 2). This reduced exercise capacity affects these patients’ independence in performing daily activities (3). Although it was shown that exercise capacity related physical status, it is not quite clear that relationship between exercise capacity and patients’ psychosocial variables in patients with fibromyalgia. Objectives To identify whether there is any direct link between the exercise capacity of women with fibromyalgia and their psychosocial status. Methods Nineteen women with fibromyalgia meeting the criteria of the American College of Rheumatology were included in the preliminary cross-sectional study (age=46.26±6.25 years, BMI=27.64±3.86 kg/m 2 ). Exercise capacity was assessed by 6-min walking test. For psychosocial variables, alexithymia, fatigue, self-efficacy, and social support were measured by Toronto Alexithymia Scale, Multidimensional Fatigue Index, General Self-Efficiacy Scale, and MOS Social Support Survey, respectively. Spearman’ correlation was used to investigate the relationship. Results The average distance walked was 468.15± 57.50 m. It was found that a significant correlation between 6-min walking test and alexithymia (r=-.517, p=. 023), fatigue (r=-.475, p=.040), and self-efficacy scores (r=.607, p&lt;.001). However, no link was observed between 6-min walking test and social support scores (r=.170, p=.486). Conclusion As a result of our study, the exercise capacity of fibromyalgia patients was reduced as in other studies. there was a strong positive correlation between exercise capacity and self-efficacy in patients with fibromyalgia. Furthermore, exercise capacity was negatively associated with multidimensional fatigue scores and alexithymia. In the light of all this, it may be said that exercise capacity is related to patients’ psychosocial status in women with fibromyalgia. We think that the structure of exercise programs aimed at improving the exercise capacity of patients should include strategies that also improve psychosocial factors. References [1]Valkeinen H, Hakkinen A, Alen M, Hannonen P, KukkonenHarjula K, Häkkinen K. Physical fitness in postmenopausal women with fibromyalgia. Int J Sports Med. 2008; 29(5): 408- 13. [2]Sener U, Ucok K, Ulasli AM, Genc A, Karabacak H, Coban NF, Simsek H, Cevik H. Evaluation of health-related physical fitness parameters and association analysis with depression, anxiety, and quality of life in patients with fibromyalgia. Int J Rheum Dis. 2013. doi: 10.1111/1756-185X.12237. [3]Mannerkorpi K, Burckhardt CS, Bjelle A. Physical performance characteristics of women with fibromyalgia. Arthritis Rheum. 1994; 7(3): 123-29. Disclosure of Interests None declared
A theory-based practical solution to correct for sex-differential participation bias
Authors: Hanbin Lee, Buhm Han
Journal: Genome biology (2022)

Abstract Most genomic cohorts are retrospective where the exposures and outcomes are predetermined prior to sample collection. Therefore, a spurious association between an exposure and an outcome can arise if both variables affect study participation. Such concerns were raised in previous studies questioning the representativeness of the UK Biobank. Recently, a genome-wide association study (GWAS) on biological sex found many autosomal hits and non-negligible autosomal heritability which the authors attribute to selection bias. In this study, we propose a simple and a practical method that can overcome sex-driven selection bias based on theoretical analysis and simulations.
AB0573 PERIPHERAL BLOOD B-CELLS SUBSETS IN PATIENTS WITH SJOGREN’S SYNDROME DEPENDING ON SOME IMMUNOLOGICAL PARAMETERS.
Authors: A. Torgashina, E. Sokol, B. Chalcev, J. Khvan, M. Kireeva, D. Tabakov, A. Aleksankin, S. Glukhova
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To examine В-cell subsets in peripheral blood of Sjogren`s syndrome (SjS) patients (pts) and to analyze the association between B-cell subsets and different clinical and immunological parameters. Methods 67 active SjS pts (65F/2M); mean age 51±14,4 years; disease duration 60 (24-120) months were included. SjS was diagnosed based on the ACR-EULAR2016 criteria. Twenty healthy donors composed the control group. CD19+B cells, memory B-cells (CD19+CD27+), non-switched memory B-cells (CD19+IgD+CD27+), switched memory B-cells (CD19+IgD-CD27+), naïve (CD19+IgD+CD27-), double negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38+) B-cells, plasmablasts (CD19+СD38+++IgD-CD27+) were analyzed by multicolor flow cytometry using cytometer Navios (Beckman Coulter, USA). The nonparametric Mann-Whitney test, the Pearson`s x2 criterion, Spearman rank correlation coefficient were used for statistical analysis. Data were shown as median (Me) with an interquartile range of 25 - 75 percentile. The differences were considered statistically significant when p&lt;0.05. Statistica 10 for Windows (StatSoft Inc., USA) package was used for statistical data processing. Results The percentages/absolute numbers of plasmablasts, transitional B-cells, memory B-cells in SjS were significantly higher than in healthy donors, p&lt;0.01 for all cases. At the same time percentages/absolute numbers of naïve cells in SjS were reduced compared to healthy donors (p=0.005, p=0.04). Shorter duration of SjS (less than 2 years) correlated with higher rates of naïve cells (p=0.02). ESSDAI score was ≥5 in 33 pts and &lt;5 in 34 pts. We didn`t find any correlation between B cells subsets and disease activity. The presence of lymphoma in pts (n=5) had no impact on B-cells subsets as well. Significant changes were in B-cells subsets were found depending on immunological parameters. Pts with an isolated increase of antinuclear antibodies (ANA) (ANA positive, RF/aRo/aLa negative) had no plasmablasts in peripheral blood, level of plasmablasts in other pts was 1.5 (1-4.5)x10 3 /µL, р=0,004. ARo-positive pts had higher amount of plasmablasts and transitional B-cells than aRo-negative pts (2 (1-5) and 1 (0-1) x10 3 /µL, p= 0.004). Higher level of plasmablasts and transitional B-cells also correlated with decrease in C3 and/or C4 (p≤0.03) and increase in IgG (p&lt;0.025). Conclusion According to our data elevated level of plasmablasts and transitional B-cells had positive correlation with some immunological diagnostic markers and immunological activity parameters of SjS but didn`t associate with ESSDAI. Disclosure of Interests None declared
To stent or not to stent: do we have an answer yet?
Authors: Jahnvi Dhar, Anurag Sachan, Jayanta Samanta
Journal: Endoscopy (2022)

See also: Reply to Dhar et al.Endoscopy 2022; 54(07): 729-729DOI: 10.1055/a-1855-6975 See also: Impact of transmural plastic stent on recurrence of pancreatic fluid collection after metal stent removal in disconnected pancreatic duct: a randomized controlled trialEndoscopy 2022; 54(09): 861-868DOI: 10.1055/a-1747-3283
POS0590 ASSOCIATIONS BETWEEN SELF-REPORTED RHEUMATOID ARTHRITIS, RHEUMATOID FACTOR POSITIVITY AND STRUCTURAL BRAIN PHENOTYPES IN UK BIOBANK
Authors: I. Stanciu, S. Siebert, D. Mackay, D. Lyall
Journal: Annals of the Rheumatic Diseases (2022)

Background There is very limited research on structural brain health in people with rheumatoid arthritis (RA). Objectives To investigate whether there are differences in brain volume in people with self-reported RA or positive rheumatoid factor (RF+). Methods Cross-sectionally tested for associations with several MRI brain volume measures in UK Biobank (n=37,379 of whom 432 RA and 1833 RF+). The partially adjusted regression models controlled for age and sex, while the fully adjusted models further controlled for deprivation index, smoking status and cardiometabolic diseases. For all subcortical volumes analyses we also controlled for total brain volume. Results Those that self-reported RA were more likely to have increased WMH (White Matter Hyperintensities) (β= 0.08, 95% CI= 0.022; 0.14, p&lt;0.01), and smaller volumes of the amygdala (β=-0.09, 95% CI= -0.16; -0.02, p&lt;0.01), pallidum (β=-0.07, 95% CI= -0.13; -0.005, p&lt;0.05) and thalamus (β= -0.06, 95% CI= -0.12; -0.01, p&lt;0.05) in the partially adjusted analyses. In the fully adjusted model only amygdala volume remained negatively associated with RA (β=-0.09, 95% CI= -0.16; -0.02, p&lt;0.01). Conclusion We provide evidence of differences in structural brain phenotypes known to underpin cognitive and psychological health, in RA. Since the amygdala may play an important role in pain modulation and mental health, while WMH are associated with a higher risk of stroke, the observed differences may be of clinical relevance in RA which is associated with a higher prevalence of these conditions. Further research is required to confirm these findings and asses their functional implications. Disclosure of Interests None declared.
AB0471 FIRST SYMPTOMS AT THE ONSET OF PRIMARY SJÖGREN’S SYNDROME – THE PATIENTS’ PERSPECTIVE OF A SNEAKY DISEASE
Authors: A. Lackner, J. Fessler, S. Zenz, J. Hermann, J. Thiel, M. Stradner
Journal: Annals of the Rheumatic Diseases (2022)

Background Primary Sjögren Syndrome (PSS) is an autoimmune disorder with a diverse spectrum of clinical manifestations ranging from sicca symptoms to severe systemic organ involvement. Little is known about the symptoms at the onset of PSS, as these are often ignored by both, patients and physicians leading to a substantial delay of diagnosis. Objectives The aim of this study was to investigate patients’ recollection of the first symptoms before diagnosis of PSS in qualitative interviews. The second aim was to verify and quantify these aspects in a representative cohort. Methods All PSS patients fulfilled the EULAR/ACR 2016 classification criteria. In the first part of the study, consecutive PSS patients were recruited for individual, semi-structured interviews. A discussion guide with five open-ended questions was developed to explore patients’ experiences on the onset of PSS. All interviews were audio-recorded and transcribed verbatim, and an inductive thematic data analysis was performed using MAXQDA software (VERBI, Berlin, Germany). In the second part, the identified aspects of the qualitative analysis were grouped to a checklist with ten items. Patients were asked to complete the checklist before their routine clinical assessment. Results One-hundred and thirty-four patients participated in the study. The qualitative part was completed by 31 PSS patients; 90.3% (n=28) were female and patients had a mean disease duration of 6.9 years (±5.7(SD)) and a mean age of 58.1 years (±12.6). Four different major aspects emerged of how patients experienced the beginning and first symptoms of PSS: (1) sicca symptoms started after initial swelling of parotis and/or lymph nodes (2) “Classic” PSS symptoms (fatigue, pain, dryness): patients reported wandering joint pain before diagnosis with a long time apart from first symptoms until diagnosis. Patients described joint pain, chronic malaise, and fatigue over months. (3) Hormonal changes (e.g. after birth, hysterectomy) or infections before the onset of PSS symptoms. (4) Slowly progressing discomfort due to sicca: patients reported a slow progression of symptoms with no initial recognition of sicca discomfort. In these patients recurrent dental problems and loss of teeth in the years prior to diagnosis was common. In the second part of the study, the four themes were verified in an independent cohort of 103 PSS patients. Patients were 59.9 (±13.7) years old and six patients were male. The main symptom before diagnosis was dryness (n=77, 74.8%) with wandering joint pain (n=51, 49.5%) and fatigue (n=47, 45.6%). In 38.8% (n=40), patients reported a swelling/inflammation of the parotid gland at the onset of disease. Conclusion We identified four themes describing the initial symptoms of PSS. Raising awareness of these symptoms among physicians and among the general public may allow earlier diagnosis of PSS. Disclosure of Interests None declared
AB0701 Frequency and risk factors of osteoporosis in men with systemic scleroderma
Authors: A. Sorokina, O. Dobrovolskaya, N. Demin, N. Toroptsova
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To identify the frequency and risk factors of osteoporosis (OP) in men with systemic scleroderma (SSc). Methods 37 men with SSс were enrolled in the study: 19 (51,4%) with limited and 18 (48,6%) with diffuse cutaneous subtype. Patients with overlap rheumatic syndromes were not included. The median age was 56,0 [46,0; 61,0] years, the median duration of the disease was 6,0 [3,0; 9,0] years. 31 (83,8%) patients were treated with glucocorticoids (GC) &gt; 3 months, the median duration of GC use was 3,7 [2,0; 7,0] years. Dual energy X–ray absorptiometry (DXA) of the lumbar spine (LS), the femoral neck (FN) and the total hip (TH) was performed. Osteoporosis (OP) was diagnosed with a T-score &lt; -2.5 SD and osteopenia – with a T-score from -1SD to -2.5 SD at any region of interest. Z-score &lt; -2 SD was used for diagnosis of OP in men &lt; 50 years old. Spearman correlation between BMD and different factors was performed. Traditional and specific risk factors for OP were analyzed using univariate logistic regression analysis. Results The median LS BMD was 1,13 [1,03; 1,26] g/cm2, the FN BMD 0,95 [0,84; 0,99] г g/cm2 and the TH BMD - 0,99 [0,93; 1,06] g/cm2. Low BMD at least in one region of interest was detected in 19 (51,4%) patients: OP – in 8 (21,6%) (6 persons 50 years and older and 2 men &lt; 50 years); osteopenia – in 11 (29,7%) men, without significant difference between the subtypes of the disease (p&gt;0,05). 9 (24,3%) men had a history of low-trauma fracture, among them 2 (22,2%) patients had OP, 3 (33,3%) - osteopenia and 4 (44,4%) persons - normal BMD. 5 (27,8%) men with diffuse form and 3 (15,8%) - with limited cutaneous subtype had OP (p&gt;0,05). BMD in the LS correlated with uric acid (UA) (Rs = 0,59, p&lt;0.05), BMD in the FN and BMD in the TH - with duration of the disease (Rs = -0,39, p&lt;0.05 and Rs = -0,42, p&lt;0.05, respectively), with duration of GC intake (Rs = -0,46, p&lt;0.05 and Rs = -0,51, p&lt;0.05, respectively), with the level of alkaline phosphatase (AP) (Rs = -0,54, p&lt;0.05 and Rs = -0,46, p&lt;0.05). In univariate logistic regression analysis, we found out that only the force vital capacity (FVC) was associated with OP (OR 15,19 [1.15; 199.79], p=0,04). There was no association between OP and other factors such as the duration of the disease or GC intake, the level of UC and AP. Conclusion OP was found in 21.6% of men with SSc. There was no statistically significant difference in the frequency of OP depending on the subtype of the disease. Among analyzed factors, only the FVC was positive associated with OP. Further research is needed. Disclosure of Interests None declared
AB0313 CLINICAL FEATURE OF 100 CASES OF METHOTREXATE ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS WITH RA PATIENT
Authors: T. Kameda, Y. Ushio, S. Nakashima, H. Shimada, R. Wakiya, M. Kato, T. Miyagi, K. Sugihara, R. Mino, M. Mizusaki, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2022)

Background Lymphoproliferative disorders (LPDs), including malignant lymphoma, are known to occur in RA patients treated with disease modified antirheumatic drugs (DMARDs). In particular, LPD associated with methotrexate (MTX)-treated RA is often referred to as MTX-associated LPD (MTX-LPD). MTX-LPD have various clinical feature and histological findings 1) . We have accumulated MTX-LPD cases in patients with rheumatoid arthritis (MTX-RA-LPD). Objectives We clarified the clinical characteristics of MTX-RA-LPD. In addition, we examine the prognosis of MTX-LPD in RA patients. Methods We enrolled 100 RA patients who diagnosed MTX-LPD from 2005 to 2021. We collected as follow data based on clinical reports retrospectively; 1) age, 2) gender, 3) duration from RA onset to LPD onset, 4) total dose of MTX, 5) duration of MTX administration, 6) presence of extranodal lesion 7) histological findings, 8) treatment for LPD, 9) 5-year survival rate. Results The mean age of 100 MTX-RA-LPD patients (M:F=30:70) were 66.7 ± 10.7 years old, and the duration from RA onset to LPD onset were 25.2 ± 11.0 years. The total dose of MTX and duration of MTX administration were over 2,600mg and over 5 years, respectively. The extranodal lesions were found in 51%, and diffuse large B cell lymphoma was the most common histological findings. Spontaneous regression was observed in 68%. The 5-year survival rate of MTX-RA-LPD was as high as over 85%. Conclusion The clinical features of MTX-RA-LPD were similar to those previous reports. Furthermore, we suggested a good prognosis for MTX-RA-LPD. References [1]Harigai M. Lymphoproliferative disorders in patients with rheumatoid arthritis in the era of widespread use of methotrexate: A review of the literature and current perspective. Mod Rheumatol. 2018 Jan;28(1):1-8. Disclosure of Interests None declared
POS0416 PRECLINICAL EFFICACY OF AN OXAZOLOPYRIDINE IRAK4 INHIBITOR IN RODENT MODELS OF INFLAMMATION
Authors: A. Ugolkov, R. Von Roemeling, R. Martell
Journal: Annals of the Rheumatic Diseases (2022)

Background Interleukin-1 receptor-associated kinase 4 (IRAK-4) is involved in Toll-Like Receptor (TLR) and Interleukin-1 Receptor (IL-1R) signaling pathways regulating innate immunity. Inhibition of IRAK4 could block the expression of cytokines involved in autoimmune disorders such as rheumatoid arthritis. CA-4948 is a member of the oxazolopyridine class of IRAK4 inhibitors and has been shown to suppress TLR agonist-induced NF-kappaB activation, TNF-alpha and IL-1beta expression in the THP-1 monocytic cell line. Objectives Determine whether a highly specific oxazolopyridine IRAK4 inhibitor demonstrates efficacy in mouse models of arthritis and systemic inflammation; compared to an isoquinoline inhibitor PF-06650833. Methods We used the mouse model of collagen induced arthritis (CIA) and lipopolysaccharide (LPS)-induced cytokine release mouse model of systemic inflammation. Mice were treated with CA-4948 or PF-06650833. In the CIA mouse model, disease activity was determined by measuring inflammation swelling in the affected joints (paw volume) and clinical score over time. Histopathological evaluation of the sum of hindpaws was performed for CIA study. A single oral dose of IRAK4 inhibitor was administered to CD-1 mice followed by intraperitoneal administration of LPS at 3 hours. ELISA kits were used to evaluate cytokine levels in mouse serum samples at 1 and 3 hours after LPS challenge. Results Treatment with CA-4948 or PF-06650833 resulted in inhibition of arthritis severity in the CIA mouse model and a decreased expression of proinflammatory cytokines as measured in mouse blood after LPS challenge. Consistent with CIA in-life data, treatment with CA-4948 decreased the score of all histopathological parameters (inflammation, cartilage erosion, synovial hyperplasia and pannus, bone degeneration/resorption, periosteal/exostotic changes, and composite scores) when compared to vehicle control and the differences attained statistical significance for all histopathological parameters. Treatment with CA-4948 resulted in a significant reduction of cytokine levels by 72% for TNF-alpha and 35% for IL-6 in LPS-induced cytokine release mouse model. Conclusion A highly specific oxazolopyridine IRAK4 inhibitor, CA-4948, demonstrated potent therapeutic efficacy in mouse models of arthritis and systemic inflammation. Disclosure of Interests Andrey Ugolkov Employee of: I am employed by Curis., Reinhard von Roemeling Employee of: I am employed by Curis, Robert Martell Employee of: I am employed by Curis.
Metabolic Regulation of Hematopoietic Stem Cells
Authors: Claudia Morganti, Nina Cabezas-Wallscheid, Keisuke Ito
Journal: HemaSphere (2022)

Cellular metabolism is a key regulator of hematopoietic stem cell (HSC) maintenance. HSCs rely on anaerobic glycolysis for energy production to minimize the production of reactive oxygen species and shift toward mitochondrial oxidative phosphorylation upon differentiation. However, increasing evidence has shown that HSCs still maintain a certain level of mitochondrial activity in quiescence, and exhibit high mitochondrial membrane potential, which both support proper HSC function. Since glycolysis and the tricarboxylic acid (TCA) cycle are not directly connected in HSCs, other nutrient pathways, such as amino acid and fatty acid metabolism, generate acetyl-CoA and provide it to the TCA cycle. In this review, we discuss recent insights into the regulatory roles of cellular metabolism in HSCs. Understanding the metabolic requirements of healthy HSCs is of critical importance to the development of new therapies for hematological disorders.
Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes
Authors: Gerasimos Filippatos, Javed Butler, Dimitrios Farmakis, Faiez Zannad, Anne Pernille Ofstad, João Pedro Ferreira, Jennifer B. Green, Julio Rosenstock, Sven Schnaidt, Martina Brueckmann, Stuart J. Pocock, Milton Packer, Stefan D. Anker
Journal: Circulation (2022)

Background: Empagliflozin improves outcomes in patients with heart failure with a preserved ejection fraction, but whether the effects are consistent in patients with and without diabetes remains to be elucidated. Methods: Patients with class II through IV heart failure and a left ventricular ejection fraction &gt;40% were randomized to receive empagliflozin 10 mg or placebo in addition to usual therapy. We undertook a prespecified analysis comparing the effects of empagliflozin versus placebo in patients with and without diabetes. Results: Of the 5988 patients enrolled, 2938 (49%) had diabetes. The risk of the primary outcome (first hospitalization for heart failure or cardiovascular death), total hospitalizations for heart failure, and estimated glomerular filtration rate decline was higher in patients with diabetes. Empagliflozin reduced the rate of the primary outcome irrespective of diabetes status (hazard ratio, 0.79 [95% CI, 0.67, 0.94] for patients with diabetes versus hazard ratio, 0.78 [95% CI, 0.64, 0.95] in patients without diabetes; P interaction =0.92). The effect of empagliflozin to reduce total hospitalizations for heart failure was also consistent in patients with and without diabetes. The effect of empagliflozin to attenuate estimated glomerular filtration rate decline during double-blind treatment was also present in patients with and without diabetes, although more pronounced in patients with diabetes (1.77 in diabetes versus 0.98 mL/min/1.73m 2 in patients without diabetes; P interaction =0.01). Across these 3 end points, the effect of empagliflozin did not differ in patients with prediabetes or normoglycemia (33% and 18% of the patient population, respectively). When investigated as a continuous variable, baseline hemoglobin A1c did not modify the effects on the primary outcome ( P interaction =0.26). There was no increased risk of hypoglycemic events in either subgroup as compared with placebo. Conclusions: In patients with heart failure and a preserved ejection fraction enrolled in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), empagliflozin significantly reduced the risk of heart failure outcomes irrespective of diabetes status at baseline. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03057951.